The role of insulin-like growth factor-I and polyamines in developing rat small intestine

Year 2011, Volume: 70 Issue: 2, 13 - 24, 27.10.2011

Ömür Karabulut-bulan , Sehnaz Bolkent

Abstract

IGF-I, Insulin like growth factor-I is a multi-functional polypeptide which organizes the proliferation and differentiation of various cell types and has a metabolic activity similar to insulin. We know that IGF-I receptors localize in the gastrointestinal tract. Polyamines play an important role in the gastrointestinal growth which connect with IGF-I. DFMO, α-difluoromethylornithine is an irreversible inhibitor of ODC, ornithine decarboxylase, the rate-limiting enzyme in the synthesis of polyamines. In the IGF-I-promoted growth the role of polyamines mainly investigate in vitro systems, however, in vivo studies are necessary to clarify the subject. Our aim in this study is to examine the in vivo role of IGF-I as a stimulant in the growth of developing rat's small intestine, and to clarify the role of polyamines in the period of growth promoted by IGF-I. In this study, animals were divided into 2 groups. DFMO (500 mg/kg/day) was administered for 10 days to 9 rats forming the experimental group. Sterile 0.9% NaCl was injected at the same volume as for the experimental animals into 8 rats forming the control group. Tissue samples were taken from the rats for histological, immunohistochemical and biochemical analyses on the 10th day. In the group given DFMO, the expansion and compression of the villi, as well as a decrease in the PAS-positive reaction intensity of brush border and in the number of goblet cells were observed. mmunohistochemical assessments showed that the number of PCNA, ODC and IGF-I positive cells in the DFMO-treated group decreased significantly, compared with the control group. Biochemical investigations showed that DNA values in the small intestinal tissue decreased insignificantly in the DFMO treated group as compared to the control one. We concluded that application of DFMO in the developing rat small intestine inhibited polyamine synthesis and IGF-I synthesis and partially prevented growth of the intestine.
Keywords: Polyamine, α-difluoromethylornithine, insulin-like growth factor-I, ornithine decarboxylase

Keywords

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Gelişen sıçan ince bağırsağında insülin benzeri büyüme faktörü I’in ve poliaminlerin rolü

Abstract

İnsülin benzeri büyüme faktörü I (IGFI), çeşitli hücre tiplerinde ve dokularda hücre çoğalmasını ve farklılaşmasını düzenleyen, insülin gibi metabolik aktiviteye sahip olan çok fonksiyonlu bir polipeptiddir. IGF-I reseptörlerinin gastrointestinal kanalda bulunduğu bilinmektedir. -Difluoromethlornitine (DFMO), intraselüler poliamin sentezinin anahtar enzimi olan ornithine dekarboksilaz’ın (ODC) spesifik bir inhibitörüdür. Poliaminler, IGF-I ile ilgili gastrointestinal büyümede önemli bir rol oynarlar. IGF-I’in teşvik ettiği büyümede poliaminlerin rolü eses olarak in vitro sistemlerde araştırılmıştır, bununla beraber, konuya açıklık getirmek için in vivo çalışmalar gereklidir. İmmunohistokimyasal düzeyde yaptığımız, ayrıca biyokimyasal olarak da Karabulut-Bulan & Bolkent / IUFS Journal of Biology 2011, 70(2):13-24 desteklediğimiz bu çalışmada, gelişen sıçan ince bağırsağında, in vivo olarak IGF- I’in büyümeyi uyarıcı etkisini araştırmak ve IGF-I’in uyardığı büyüme süresince poliaminlerin rolüne açıklık getirmek amaçlanmıştır. Bu çalışmada, hayvanlar iki grupta toplandı. Deney grubunu oluşturan 9 sıçana 500 mg/kg DFMO (Difluoromethylornithine) 10 gün süre ile enjekte edildi. Kontrol grubundaki 8 sıçana ise aynı doz ve sürede fizyolojik su enjeksiyonu yapıldı. Histolojik, immunohistokimyasal ve biyokimyasal analizler için 10. günde sıçanlardan doku örnekleri alındı. Difluoromethylornitine (DFMO) verilen grupta villuslarda genişleme ve basıklaşma, çizgili kenardaki ve goblet hücrelerindeki PAS pozitif reaksiyonun şiddetinde ve goblet hücrelerinin sayısında azalma gözlendi. İmmunohistokimyasal değerlendirmeler, DFMO verilen grupta PCNA, ODC ve IGFI pozitif hücrelerin sayısında kontrol grup ile kıyaslandığında anlamlı bir azalma olduğunu gösterdi. Biyokimyasal incelemeler ince bağırsak dokusundaki DNA değerlerinin DFMO verilen grupta kontrol grup ile kıyaslandığında anlamlı olmayan bir şekilde azaldığını gösterdi. Sonuç olarak, DFMO’nun gelişmekte olan sıçan ince bağırsağında poliamin sentezini ve IGF-I sentezini inhibe ettiğini ve bağırsak büyümesinin kısmen engellendiğini söyleyebiliriz.

Keywords

Poliamin, α-difluorometilornitin, insulin-benzeri büyüme faktörü-I, ornitin dekarboksilaz

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